The goal of this proposal is to elucidate the nature of induced polarization in condensed biomolecular systems and to complete a first generation all-atom polarizable force field for proteins and phospholipid membranes. We have adopted and started to develop a potential function that incorporates electronic polarizability using classical Drude oscillators. We have optimized a simple water model (SWM4-DP) and are now ready to move to the next phase. Our first aim will be to elucidate the nature of induced polarizability in condensed phases relative to the gas phase by optimizing the force field for a number of basic compounds. These initial studies will also help clarify the fundamental reduction of induced electronic polarizability in condensed systems caused by Pauli's exclusion principle and the overlap of electronic clouds. Our second aim will be to optimize the internal portion of the force field. Our third aim will be to assess the accuracy of the force field by performing molecular dynamics simulations of a test suite of proteins in the crystal environment. In addition, the nature of the interfacial potential of lipid membranes will be elucidated by performing a MD simulation of a fully polarizable model of a lipid bilayer and of the cation-ligand interactions giving rise to cooperative binding of calcium to the EF-hands in calbindin. It is important to emphasize that the three aims in the proposed study are linked in an iterative fashion. Upon completion of the proposed study a novel force field for proteins and lipids that includes explicit treatment of electronic polarizability will be available to the scientific community. While the proposed studies will be performed using the program CHARMM, the simplicity of the classical Drude oscillator used to treat electronic polarizability will insure that the developed force field may be readily implemented in other simulation packages.